Temporal lobe epilepsy (TLE) is the most common form of epilepsy which can become medically refractory and referred for surgery. The thalamus has been shown to demonstrate both structural and functional changes in TLE. However, little is known about microstructural alterations within individual thalamic nuclei. In this study, we used diffusion tensor imaging (DTI) to determine if subjects with unilateral TLE demonstrate hemispheric and intra-hemispheric differences in thalamic nuclei across clinical characteristics. We report statistically significant differences in nuclei in subjects with tonic-clonic seizures and mesial temporal sclerosis in both hemispheric and intra-hemispheric comparisons.